2-Chloromethyl-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine hydrochloride

Product Description

2-Chloromethyl-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine hydrochloride is an organic compound with a complex structure and specific applications. It is a derivative of pyridine, featuring a chloromethyl group at the 2-position, a methyl group at the 3-position, and a trifluoroethoxy group at the 4-position, all in the form of a hydrochloride salt. 2-Chloromethyl-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine hydrochloride typically appears as a white to pale yellow solid. It can be synthesized through methods such as N-oxidation with peracetic acid in acetic acid or microwave-assisted reactions with 2-mercaptobenzimidazole and anhydrous sodium carbonate. It is primarily used as an intermediate in the synthesis of proton pump inhibitors like lansoprazole and dexamethasone.

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Product Use & Characteristics

Molecular Information

• Molecular Formula: C₉H₁₀Cl₂F₃NO

• Molecular Weight: 276.08 g/mol

• IUPAC Name: 2-(chloromethyl)-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine; hydrochloride

Structure

• Core Structure: Pyridine ring

• Substituents:

  • 2-Position: Chloromethyl (-CH₂Cl)

  • 3-Position: Methyl (-CH₃)

  • 4-Position: 2,2,2-Trifluoroethoxy (-OCH₂CF₃)

• Salt Form: Hydrochloride (enhances water solubility and stability)

Chemical Classification

• Type: Heterocyclic compound → Pyridine derivative

• Functional Groups:

  • Alkyl halide (chloromethyl)

  • Ether (trifluoroethoxy)

  • Trifluoromethyl group (highly electronegative, lipophilic)

  • Salt form (hydrochloride)

Synthesis Methods

1. N-Oxidation Reaction:

   • Dissolve 2-chloromethyl-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine hydrochloride in acetic acid.

   • Heat to 80-85°C and add peracetic acid dropwise.

   • Allow the reaction to proceed for 2-3 hours and monitor completion by thin-layer chromatography (TLC).

2. Microwave-Assisted Reaction:

   • Mix equimolar amounts of 2-chloromethyl-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine hydrochloride, 2-mercaptobenzimidazole, and anhydrous sodium carbonate.

   • Irradiate in a 600-watt microwave oven for 2-10 minutes.

   • Cool, dissolve in methanol, and purify by silica gel column chromatography.

3. General Approach:

   • Start with a 3-methyl-4-hydroxypyridine derivative.

   • Alkylate the 4-position with 2,2,2-trifluoroethyl halide (e.g., CF₃CH₂I) in the presence of a base.

   • Introduce the chloromethyl group at position 2 via chloromethylation (e.g., using formaldehyde/HCl or CH₂O/PCl₃).

   • Form the hydrochloride salt by treating with HCl (gas or in a solvent like ether).

Physical and Chemical Properties

• Appearance: White to off-white crystalline powder

• Solubility: Water-soluble in salt form; soluble in polar organic solvents (e.g., ethanol, acetonitrile)

• Stability: Stable under dry conditions; hydrolyzable under strong acid/base

• Melting Point: 208-214 °C

• LogP: 2.692 (more soluble in non-polar solvents)

Uses

• Pharmaceutical Intermediates: Used as an important intermediate to synthesize drug molecules with specific pharmacological activities, such as proton pump inhibitors (e.g., lansoprazole) and other drugs with antibacterial, antiviral, or antitumor activities.

• Pesticide Intermediates: Used in the synthesis of new pesticide active ingredients, such as insecticides or fungicides.

• Fluorine Introduction: Useful for incorporating fluorine in medicinal chemistry to enhance drug bioavailability or metabolic stability.

Safety and Handling

• Hazards:

  • Chloromethyl group may cause skin/eye irritation and is potentially harmful if inhaled or ingested.

  • Trifluoroethoxy ethers may pose environmental concerns due to persistence.

• Precautions:

  • Use gloves, eye protection, and work in a fume hood.

  • Store in a cool, dry, well-ventilated area, away from strong acids or bases.

  • In case of accidental contact or inhalation, take appropriate first aid measures and seek medical attention immediately.

Storage Conditions

• Store in a cool, dry, well-ventilated place, avoiding direct sunlight and high temperatures.

• Store in a sealed container to prevent reaction with moisture, oxygen, etc., and avoid volatile losses.

Related Compounds

• 2-Chloromethylpyridines

• Fluoroalkylated pyridine derivatives

• Intermediates in drugs like fluoroquinolones or anthelmintics

Safety Information

• Hazard Statements: Causes serious eye damage, may cause an allergic skin reaction.

• Precautionary Statements:

  • Avoid breathing dust/fume/gas/mist/vapors/spray.

  • Contaminated work clothing should not be allowed out of the workplace.

  • Wear protective gloves/eye protection/face protection.

  • Wash contaminated clothing before reuse.

  • Dispose of contents/container to an approved waste disposal plant.

• First Aid Measures:

  • Inhalation: Move to fresh air. If breathing is difficult, give oxygen. If not breathing, give artificial respiration and consult a doctor immediately.

  • Skin Contact: Take off contaminated clothing immediately. Wash off with soap and plenty of water. Consult a doctor.

  • Eye Contact: Rinse with pure water for at least 15 minutes. Consult a doctor.

  • Ingestion: Rinse mouth with water. Do not induce vomiting. Never give anything by mouth to an unconscious person. Call a doctor or Poison Control Center immediately.

• Handling and Storage: Handle in a well-ventilated area. Store in a tightly closed container in a dry, cool, and well-ventilated place, away from incompatible substances and sources of ignition.

• Personal Protective Equipment (PPE): Wear tightly fitting safety goggles with side-shields, fire/flame-resistant and impervious clothing, and chemical-impermeable gloves. If exposure limits are exceeded or irritation occurs, use a full-face respirator.

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Qingdao Sigma Chemical Co., Ltd., established in January 2017 and headquartered in Qingdao, China, is a reliable chemical supplier. Specializing in pharmaceuticals, biochemical intermediates, and research chemicals, the company offers a diverse product portfolio, including peptides (e.g., Tirzepatide, Semaglutide), nootropics, veterinary products, and APIs, often marketed with ≥99% purity and COA certification. We provides R&D, custom synthesis, and contract manufacturing services at various scales, while claiming a global export presence across 100+ countries. With international warehouses in the USA, Europe, Australia, and Canada, Qingdao Sigma Chemical also facilitates drop-shipping and reshipments, positioning itself as a key supplier for laboratory and research applications.